New drug helps control rare sarcoma disease

The experimental agent cediranib shrank tumors in more than half of study subjects afflicted with alveolar soft part sarcoma (ASPS). This rare, slow-growing cancer forms in tissues that connect, support, or surround organs. It accounts for less than 1% of all soft tissue sarcomas and usually strikes children and young adults, manifesting as a painless mass in the leg or buttock. There is no effective systemic treatment for metastatic disease.

Cediranib, a potent oral inhibitor of vascular endothelial growth factor receptor (VEGFR-1, -2, -3) tyrosine kinases, blocks the formation of new blood vessels. The drug has been tested in the treatment of lung, colorectal, and other tumors, but ASPS is the first solid tumor that has demonstrated substantial shrinkage, according to a statement from the National Cancer Institute (NCI), whose scientists carried out the ASPS phase II clinical trial.

Of 36 enrolled patients, ranging in age from 19 to 59 years, 28 were evaluable by the time the NCI's Shivaani Kummar, MD, and colleagues presented their findings at the annual meeting of the American Society of Clinical Oncology (ASCO), held June 3-7, 2011, in Chicago, Illinois (http://abstract.asco.org/AbstView_102_78928.html). The subjects had received cediranib 30 mg by mouth once a day in 28-day cycles. More than half had tumor shrinkage: More specifically, 12 patients (43%) had a partial response; four had a greater than 20% reduction in target lesions; and six others were stable at 6 months. These outcomes translated to a disease-control rate at 6 months of 78% (22 of 28 patients). Some patients continued to receive treatment for more than a year.

“It is unusual to see such high levels of tumor shrinkage in a cancer that traditionally has not responded to standard chemotherapy used for the treatment of sarcomas,” noted Kummar, the head of early clinical trials development for the NCI Division of Cancer Treatment and Diagnosis.

Common toxicities (grade 2 or higher) of cediranib included transaminitis, hypertension, diarrhea, tumor pain, and proteinuria. According to NCI, these side effects were manageable.

NCI is planning a follow-up study to confirm these promising results. The upcoming trial will compare cediranib with sunitinib—another inhibitor of blood vessel growth—in persons with ASPS.